Figure 6.
Microglial derived macrophages may induce mesenchymal transformation and evidence for T-cell exhaustion and tumor permissive immune microenvironment. a. Correlations between tumor and immune cell types show microglia-associated macrophages are enriched and monocyte-associated macrophages depleted in Mes subtype; FDR (q < 0.05) for all data points; b. Heatmap of immune cell types shows microglial cells are enriched in mesenchymal adult HGG gene set; FDR < 0.05; c. Nearest neighbor analysis using immunofluorescence shows Mes (IGFBP2+) cells are on average closer to microglial derived type 2 macrophages (CD163+/CD74−) than to OPCs (Olig2+); data points show statistical mode by sample; total number of cells analyzed exceeds 290 for each sample, representative IF images in Supplementary Figure S3d; d. Microglia-derived macrophage (micro) population has greater proportion of M2 macrophages than CD14+ or CD16+ monocyte-associated macrophages; e. M1 (HLA-DPA1, C3) and M2 (CD163) markers validate macrophage classification by gene expression; f. Marker gene expression suggests T-cell exhaustion; exhaustion markers (CD44, SPN, CD69, PRDM1 are enriched), while enrichment markers (IL7R, SELL, GZMB) are depleted; g. GSEA showing negative NES for gene sets upregulated during tumor rejection suggests tumor permissive immunosuppressed microenvironment.

Microglial derived macrophages may induce mesenchymal transformation and evidence for T-cell exhaustion and tumor permissive immune microenvironment. a. Correlations between tumor and immune cell types show microglia-associated macrophages are enriched and monocyte-associated macrophages depleted in Mes subtype; FDR (q < 0.05) for all data points; b. Heatmap of immune cell types shows microglial cells are enriched in mesenchymal adult HGG gene set; FDR < 0.05; c. Nearest neighbor analysis using immunofluorescence shows Mes (IGFBP2+) cells are on average closer to microglial derived type 2 macrophages (CD163+/CD74) than to OPCs (Olig2+); data points show statistical mode by sample; total number of cells analyzed exceeds 290 for each sample, representative IF images in Supplementary Figure S3d; d. Microglia-derived macrophage (micro) population has greater proportion of M2 macrophages than CD14+ or CD16+ monocyte-associated macrophages; e. M1 (HLA-DPA1, C3) and M2 (CD163) markers validate macrophage classification by gene expression; f. Marker gene expression suggests T-cell exhaustion; exhaustion markers (CD44, SPN, CD69, PRDM1 are enriched), while enrichment markers (IL7R, SELL, GZMB) are depleted; g. GSEA showing negative NES for gene sets upregulated during tumor rejection suggests tumor permissive immunosuppressed microenvironment.

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